Going Gently into Flight: Analyzing Noncovalent Interactions by Mass Spectrometry

Dedicated to Professor John Fenn, recipient of the 2002 NobelPrize in Chemistry, for his extraordinary contributions to the development and implementation of electrospray mass spectrometry in the true spirit of scientific discovery and fun. Historically, mass spectrometry came of age during the heydey of organic chemicalanal ysis and structure determination, when the identification of molecular ions and their fragments complemented the fingerprinting of specific chemicalfunctionalgroups by infrared and ultraviolet spectroscopies. As ever larger (i.e., > 1000 Da) and more complex structures were characterized, increasingly by the use of NMR, mass spectrometry (MS) also rose to the challenge, with the development of newer ionization methods, including fast-atom bombardment 1 and matrix-assisted laser desorption ionization (MALDI) 2 techniques, as well as tandem 3 and secondary ion 4 mass spectrometry. Along the way, MS also made fundamental contributions to many other areas of chemistry, ranging from physicalstudies of the structures of gas-phase ions and their behavior, 5 to biological investigations of enzymatic reactions and other metabolic processes. 6